Disruption of neurosteroid synthesis and release by tris(2,3-dibromopropyl)isocyanurate in primary mouse cortical astrocytes in vitro

Neurosteroidogenesis in astrocytes is crucial for the proper development and functioning of the brain. During this process, key neurohormones such as progesterone (P-4), testosterone (T), and estradiol (E-2) are produced. Proper production and release of neurosteroids can be affected by substances referred to as endocrine-disrupting compounds (EDCs). Tris-(2,3-dibromopropyl)isocyanurate (TBC) is a representative of novel brominated flame retardants used to stop ignition or reduce fire-related property damage to plastics, polyolefin, polyphenyl alkene, unsaturated polyester, synthetic rubber, and fibers. Interestingly, previous studies have shown that TBC can enhance the proliferation of estradiol-sensitive breast cancers in vitro, which suggests that TBC has EDC properties. Therefore, given the suspected endocrine-disrupting properties of TBC, the aim of the present study was to determine the impact of TBC on the neurosteroid (P-4, T, and E-2) production and secretion as well as the mRNA expression of key enzymes involved in its production in mouse astrocytes in vitro. Our paper shows that TBC increases P-4 production with a strong decrease in T production, which is accompanied by a decrease in Cyp17a1 mRNA expression, that is, the main enzyme metabolizing P-4 to T. Moreover, TBC in both studied concentrations increases P-4 secretion in the culture medium. Finally, our studies have demonstrated an increase in the expression of Cyp19a1 mRNA, an enzyme metabolizing T to E-2, with a simultaneous increase in the amount of E-2 in cells. Our data clearly show that TBC in an in vitro environment acts as EDCs, which may lead to serious consequences for the proper development and functioning of the brain.

Automated summary

Neurosteroidogenesis in astrocytes is important for brain development and functioning. The production and release of key neurohormones can be affected by endocrine-disrupting compounds (EDCs) such as TBC. This study aimed to investigate the impact of TBC on neurosteroid production, secretion, and mRNA expression of key enzymes. The results showed that TBC increased progesterone production and secretion, decreased testosterone production, and increased estrogen production. These findings suggest that TBC acts as an EDC and can potentially affect brain development and functioning.